Weight Control and Diet

Description

Alternative Names

Biologic and Medical Causes

Obesity results when the body consumes more calories than it uses. Research points to several different factors that may influence weight gain. About 90% of people who diet gain every pound back that they lose regardless of their weight-loss method. Some evidence suggests that every person has an inherited weight range that varies by only about 10% either up or down from some set point. (For instance, a man whose "genetically-determined" weight is 200 pounds would tend to swing from 180 to 220 pounds, but would be unlikely to lose or gain more than this.) Genetic factors that influence fat metabolism and regulate certain hormones and proteins that affect appetite may play some part in 70% to 80% of obesity cases.

The Biologic Pathway to Appetite

Appetite, and, thereby weight, is determined by processes that occur in both the brain and gastrointestinal tract. Eating patterns are regulated by feeding and satiety centers located in the hypothalamus and pituitary glands of the brain that respond to signals indicating high fat stores and hunger. A number of molecules are produced that further control this process by stimulating or suppressing appetite. In some cases, genetic factors may produce imbalances in these chemicals:

• Insulin. Insulin is a hormone that is critical in the conversion of blood sugar (glucose) into energy. The process of digestion breaks down carbohydrates from our diet into sugar molecules (of which glucose is one) and proteins from our diet into their smaller components, amino acids. Right after a meal, the amount of glucose in the blood rises and signals the release of insulin, which then pours into the bloodstream. Insulin enables the glucose and amino acids to enter cells in the body, importantly, those in the muscles. Here, insulin and other hormones direct whether these nutrients will be burned for energy or stored for future use. The inability to use insulin efficiently (insulin resistance) has been associated with both obesity and diabetes.
• Leptin. Leptin is a hormone that is released by fat cells and also possibly by cells in the stomach. It appears to play an important role in insulin resistance and fat storage in the body, but its role in obesity is unclear. The most likely scenario is that in most people, leptin levels rise as more fat is stored in the cells and signal the hypothalamus in the brain to suppress appetite. Falling levels then signal the brain to stimulate appetite. In people who are genetically deficient in leptin, however, the brain may be tricked into thinking that it is always starving because there is no leptin to suppress appetite. Such people, then, would tend to gain weight.
• Resistin. Resistin is another hormone produced by fat cells and produces resistance to the activity of insulin. Some experts believe it may help explain the role of obesity in diabetes type 2.
• Intestinal Chemicals. Specific chemicals in the intestinal tract pass signals to the brain when a person is hungry or full. Ghrelin is produced in the stomach and appears to be important in triggering the desire to eat. Peptide YY336 (PYY) is a peptide secreted in the intestine after a meal in proportion to the number of calories a person eats. It signals fullness to the brain, and deficiencies may contribute to some cases of obesity. Researchers are hoping that blocking ghrelin or infusing PYY may be possible therapies for obesity.
• Other Chemicals. Many brain chemicals are being studied for their role in appetite stimulation and weight gain. Among them are neuropeptide Y, melanocortins, agouti-related protein, and melanocyte stimulating hormone. Chemicals known as endorphins may be critical in reducing appetite and regulating energy. Cholecystokinin, a hormone released in the upper intestine that stimulates digestive juices, may work to control meal size.

Insulin is a hormone produced by the pancreas that is necessary for cells to be able to use blood sugar.

Specific Genetic Factors

Genetics may contribute directly to many cases of severe obesity in people with family histories of obesity. Genetic factors may also play indirect roles in susceptibility to being overweight in many people (such those who have slower metabolism than others). There are at least seven known genetic mutations that have been associated with specific and uncommon cases of severe obesity. A few are as follows:

• HOB1 (human obesity 1) is a recently identified gene that may contribute directly to obesity. The gene is significantly linked to high BMI in women.
• A number of variants of the leptin gene, including those that cause leptin deficiencies and obesity, have been identified.
• A gene called melanocortin-4 receptor that plays a key role in shutting off the urge to eat is defective in some families with a history of obesity.
• Researchers have also identified a mutation in a gene for a protein called proopiomelanocortin, which results in a syndrome of obesity, red hair, and deficiencies in stress hormones.
• About 5% of severely obese people have mutations that over-respond to agouti-related protein.

Genetics also determine the number of fat cells a person has, and some people are simply born with more. It should be noted that even when genetic factors are present, environmental and dietary intake are still important and controllable in the great majority of obesity cases.

The Thrifty Gene. Although genetic abnormalities may make it harder or easier to lose weight, the prevalence of obesity has dramatically increased over the past two decades, and genes cannot have changed within that short amount of time. Human metabolism evolved over centuries so that it could conserve energy and store fat during times of famine. Most cases of obesity occur now in people with normal physiology who live in industrialized nations where food is overly plentiful, and it is easy to avoid expending enough energy to burn the excess calories. One theory that combines genetic and environmental factors suggests that type 2 diabetes and the obesity that usually accompanies this disorder are derived from genetic actions that were once important for survival.

Some experts postulate the existence of a so-called "thrifty" gene, which regulates hormonal fluctuations to accommodate seasonal changes. Theoretically, it works in the following manner:

• In certain nomadic populations, hormones are released during seasons when food supplies have traditionally been low, which results in resistance to insulin and efficiently increased fat storage.
• The process is reversed in seasons when food is readily available.
• Because modern industrialization has made high-carbohydrate and fatty foods available all year long, the gene no longer serves a useful function and is now harmful because fat, originally stored for famine situations, is not used up.

Such a theory could explain the high incidence of type 2 diabetes and obesity found in Pima tribes and other Native American tribes with nomadic histories and Western dietary habits. The traditional low-fat high-fiber foods (corn, lima beans, white and yellow teparies, mesquite, and acorns) of the Pima people may have protected this genetically susceptible population in the past from the high incidence of obesity and type 2 diabetes they are experiencing now.

Medical or Physical Causes of Obesity

A number of medical conditions may contribute to being overweight, although rarely are they a primary cause of obesity.

• Some overweight people may believe their weight problem is due to hypothyroidism; patients with an underactive thyroid, however, generally show only a moderate weight increase of five to 10 pounds, mainly due to accumulation of fluid.
• Very rare genetic disorders, including Froehlich's syndrome in boys, Laurence-Moon-Biedl, and the Prader-Willi syndromes, cause obesity.
• Abnormalities or injury to the hypothalamus region in the brain can cause a condition called hypothalamic obesity.
• Cushing's disease is a rare condition caused by high levels of steroid hormones, which results in obesity, a moon-shaped face, and muscle wasting.
• Obesity is also linked with polycystic ovarian syndrome, a common hormonal disorder in women.

Click the icon to see an image of polycystic ovaries.

Effects of Certain Medications

Some prescription medications contribute to weight gain, usually by increasing appetite. Such drugs include the following:

• Corticosteroids.
• Some female hormone treatments, including some oral contraceptives (usually temporary) and certain progestins (such as Megestrol) used to treat cancer.
• Antidepressants, and other psychoactive drugs, including certain antipsychotics, lithium, and antiseizure agents (such as valproate).
• In a particularly unfortunate conflict of interest for obese individuals with type 2 diabetes, the use of insulin and insulin-stimulating drugs used to treat the condition often leads to weight gain.
• Certain anti-seizure agents used in epilepsy and bipolar disorder can cause significant weight gain.
• Certain antipsychotics.
• Although drugs are not usually the primary cause of obesity or of being overweight, some people may be mistakenly tempted to stop taking their medications without their doctors' knowledge.